Target-mediated drug disposition with drug-drug interaction, Part I: single drug case in alternative formulations

J Pharmacokinet Pharmacodyn. 2017 Feb;44(1):17-26. doi: 10.1007/s10928-016-9501-1. Epub 2017 Jan 10.

Abstract

Target-mediated drug disposition (TMDD) describes drug binding with high affinity to a target such as a receptor. In application TMDD models are often over-parameterized and quasi-equilibrium (QE) or quasi-steady state (QSS) approximations are essential to reduce the number of parameters. However, implementation of such approximations becomes difficult for TMDD models with drug-drug interaction (DDI) mechanisms. Hence, alternative but equivalent formulations are necessary for QE or QSS approximations. To introduce and develop such formulations, the single drug case is reanalyzed. This work opens the route for straightforward implementation of QE or QSS approximations of DDI TMDD models. The manuscript is the first part to introduce DDI TMDD models with QE or QSS approximations.

Keywords: Competitive; Drug–drug interaction; Target-mediated drug disposition; Uncompetitive.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Binding, Competitive
  • Chemistry, Pharmaceutical
  • Drug Interactions*
  • Humans
  • Infusions, Intravenous
  • Models, Biological*
  • Pharmaceutical Preparations* / administration & dosage
  • Pharmaceutical Preparations* / chemistry
  • Pharmacokinetics*
  • Protein Binding
  • Receptors, Drug / metabolism
  • Tissue Distribution

Substances

  • Pharmaceutical Preparations
  • Receptors, Drug